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Differential effects of the D1-DA receptor antagonist SCH39166 on positive and negative symptoms of schizophrenia

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Abstract

In the present open study the effects of the D1-dopamine antagonist SCH 39166 on positive and negative symptoms of schizophrenia (DSM-IIIR) were investigated. SCH 39166 was given orally according to a fixed dosage schedule (day 1: 25 mg b.i.d; day 4: 50 mg b.i.d.; day 7: 100 mg b.i.d; day 18: 200 mg b.i.d.; day 21: 225 mg b.i.d.). Seven patients completed 2 weeks, and five patients completed the study. The reason for premature withdrawal was lack of efficacy or refusal to take SCH 39166. In none of the patients a reduction of the BPRS or CGI score was found. As measured with the PANSS, a significant reduction was observed in the score of the negative subscale, whereas the positive symptoms scale and general psychopathology score remained unaffected. Akathisia, rigidity and hypokinesia were reported occasionally, although only mild in severity. The results of the present study do not support the hypothesis that D1-dopamine antagonists are clinically effective antipsychotics in schizophrenia, considering the fact that SCH 39166 had no effect on positive symptoms. The present study provides circumstantial evidence for an effect of SCH 39166 on negative symptoms.

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References

  • Barnett A, Chipkin RE, Cohen-Winston M, Crosby G, Fox J (1988) The profile of the new D1 selective benzonaphthazepine (SCH 391 66) in four different tests suggests that it has a low probability of producing extrapyramidal effects. Psychopharmacology 96:238 Abstract 14.41.04 (supplement)

    Google Scholar 

  • Chipkin RE, Lorio LC, MqQuade RD, Berger JG, Barnett A (1988) Pharmacological profile of SCH 39166, a dopamine D1 selective benzophthazepine with potential antipsychotic activity. J Pharmacol Exp Ther 247:1093–1102

    Google Scholar 

  • Criswell HE, Mueller RA, Breese GR (1992) Pharmacologic evaluation of SCH-39166, A- 9024, NO-0756, and SCH-23390 in neonatal-6-OHDA-lesioned rats. Neuropsychopharmacology 7 [2] 95–103

    Google Scholar 

  • Ellenbroek BA, Willemen APM, Cools AR (1989) Are antagonists of dopamine D1 receptors drugs that attenuate both positive and negative symptoms of schizophrenia? A pilot study in java monkeys. Neuropsychopharmacol 2:191–199

    Google Scholar 

  • Ellenbroek, B (1988) Animal models for schizophrenia and neuroleptic drug action. Academic Thesis, Krips Repro Meppel

  • Farde L, Halldin C, Stone-Elander S, Sedvall G (1987) PET-analysis of human dopamine receptor subtypes using [11C]-SCH 23390 and [11C]-raclopride. Psychopharmacology 92:278–284

    Google Scholar 

  • Gessa GL, Canu A, Del Zompo M, Burrai C, Serra G (1991) Lack of acute antipsychotic effect of SCH-23390, a selective dopamine D1 receptor antagonist. Lancet 337:854–855

    Google Scholar 

  • Guy W (ed) (1976) ECDEU Assessment manual for psychopharmacology: publication ADM 76-338. US Department of Health Education and Welfare, Washington, DC

    Google Scholar 

  • Hall H, Halldion C, Sedvall G (1993) Bionding of [3H]SCH 39166 to human post mortem brain tissue. Pharmacol Toxicol 72:152–158

    Google Scholar 

  • Kay SR, Opler LA (1987) The positive-negative dimension in schizophrenia: its validity and significance. Psychiatr Dev 2:79–103

    Google Scholar 

  • Kay SR, Fiszbein A, Opler LA (1987) The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr Bull 13:261–276

    Google Scholar 

  • Kay SR, Opler LA, Lindenmayer JP (1988) Reliability and validity of the Positive and Negative Syndrome Scale for schizophrenics. Psychiatry Res 23:99–110

    Google Scholar 

  • Lublin H, Gerlach J, Mørkeberg F, and the NNC study group (1994a) The potential antipsychotic effects of selective D1 antagonists evaluated in monkeys and in an open clinical study. Psychopharmacology 114:3 (Abstract 10)

    Google Scholar 

  • Lublin H, Gerlach J, Mórkeber F (1994b) Long-term treatment with low doses of the D1 antagonist NNCC 756 and the D2 antagonist raclopride in monkeys previously exposed to dopamine antagonists. Psychopharmacology 114:495–504

    Google Scholar 

  • Lynch MR (1992) Schizophrenia and the D1 receptor: focus on negative symptoms. Prog Neuropsychopharmacol Biol Psychiatry 16:797–832

    Google Scholar 

  • Marken PA, Haykal RF, Fisher JN (1992) Management of psychotropic-induced hyperprolactinemia. Clin Pharmacol 11:851–856

    Google Scholar 

  • McQuade RD, Duffy RA, Coffin VL, Barnett A (1992) In vivo binding to dopamine receptors, a correlate of potential antipsychotic activity. Eur J Pharmacol 215 [1]: 29–34

    Google Scholar 

  • Overall JE, Gorham DR (1976) BPRS: Brief Psychiatric Rating Scale. In: Guy W (ed) ECDEU asessment manual for psychopharmacology. National Institute of Mental Health, Rockville, MD, pp 157–169

    Google Scholar 

  • Overall JE, Gorham DR (1962) The Brief Psychiatric Rating Scale. Psychol Rep 10: 799–812

    Google Scholar 

  • Porter TE, Gradny D, Bunzow J, Wiles CD, Civelli O, Frawley LS (1994) Evidence that stimulatory dopamine receptor may be involved in the regulation of prolactin secretion. Endocrinology 134:1263–1268

    Google Scholar 

  • Prinssen EP, Ellenbroek BA, Stamatovic B, Cools AR (1994) The effects of haloperidol and raclopride in the paw test are influenced similarly by SCH 39166. Eur J Pharmacol 231:275–280

    Google Scholar 

  • Rittenhouse PA, Levy AD, Li Q, Bethea CL, Van de Kar LD (1993) Neurons in the hypothalamic paraventricular nucleus mediate the serotonergic stimulation of prolactin secretion via 5-HT1C/2 receptors. Endocrinology 133:661–667

    Google Scholar 

  • Seeman, PH (1987) Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse 1:133–152

    Google Scholar 

  • Simpson GM, Angus JWS (1970) A raking scale for extrapyramidal side effects. Acta Psychiat Scand (Suppl. 212) 45:11–19

    Google Scholar 

  • Sobrinho LG (1993) The psychogenic effects of prolactin. Acta Endocrinol 129 [Suppl 1]:38–40

    Google Scholar 

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Den Boer, J.A., van Megen, H.J.G.M., Slaap, B.R. et al. Differential effects of the D1-DA receptor antagonist SCH39166 on positive and negative symptoms of schizophrenia. Psychopharmacology 121, 317–322 (1995). https://doi.org/10.1007/BF02246069

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  • DOI: https://doi.org/10.1007/BF02246069

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